Wolfram Dolores, Morandi Evi M, Eberhart Nadine, Hautz Theresa, Hackl Hubert, Zelger Bettina, Riede Gregor, Wachter Tanja, Dubrac Sandrine, Ploner Christian, Pierer Gerhard, Schneeberger Stefan
Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria ; Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Biomed Res Int. 2015;2015:259160. doi: 10.1155/2015/259160. Epub 2015 Feb 12.
Advances in microsurgical techniques and immunosuppressive medication have rendered transplantation of vascularized composite allografts possible, when autologous tissue is neither available nor sufficient for reconstruction. However, skin rejection and side effects of long-term immunosuppression still remain a major hurdle for wide adoption of this excellent reconstructive technique. Histopathologic changes during acute skin rejection in vascular composite allotransplantation often mimic inflammatory skin disorders and are hard to distinguish. Hence, the identification of diagnostic and therapeutic markers specific for skin rejection is of particular clinical need. Here we present novel markers allowing for early differentiation between rejection in hind limb allotransplantation and contact hypersensitivity. Assessment of Ccl7, Il18, and Il1b expression is most indicative of distinguishing skin rejection from skin inflammatory disorders. Gene expression levels varied significantly across skin types and regions, indicating localization specific mechanism of leukocyte migration and infiltration. Expression of Il12b, Il17a, and Il1b gene expression levels differed significantly between rejection and inflammation, independent of the skin type. In synopsis of the RNA expression profile and previously assessed protein expression, the Il1 family appears as a promising option for accurate skin rejection diagnosis and, as a following step, for development of novel rejection treatments.
显微外科技术和免疫抑制药物的进步使得在自体组织无法获取或不足以用于重建时，进行血管化复合异体移植成为可能。然而，皮肤排斥反应和长期免疫抑制的副作用仍然是广泛采用这种出色重建技术的主要障碍。血管复合异体移植急性皮肤排斥反应期间的组织病理学变化常常类似炎症性皮肤病，难以区分。因此，识别皮肤排斥反应特有的诊断和治疗标志物具有特殊的临床需求。在此，我们展示了能够早期区分后肢异体移植排斥反应和接触性超敏反应的新型标志物。对Ccl7、Il18和Il1b表达的评估最有助于区分皮肤排斥反应和皮肤炎症性疾病。基因表达水平在不同皮肤类型和区域之间存在显著差异，表明白细胞迁移和浸润存在局部特异性机制。Il12b、Il17a和Il1b基因表达水平在排斥反应和炎症之间存在显著差异，与皮肤类型无关。综合RNA表达谱和先前评估的蛋白质表达来看，Il1家族似乎是准确诊断皮肤排斥反应的一个有前景的选择，接下来有望用于开发新型排斥反应治疗方法。
